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Phillygenin Suppresses Glutamate Exocytosis in Rat Cerebrocortical Nerve Terminals (Synaptosomes) through the Inhibition of Cav2.2 Calcium Channels.
Lee, Ming-Yi; Lin, Tzu-Yu; Chang, Ya-Ying; Chiu, Kuan-Ming; Wang, Su-Jane.
Afiliación
  • Lee MY; Department of Medical Research, Far-Eastern Memorial Hospital, New Taipei City 22060, Taiwan.
  • Lin TY; Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 22060, Taiwan.
  • Chang YY; Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan.
  • Chiu KM; Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 22060, Taiwan.
  • Wang SJ; International Program in Engineering for Bachelor, Yuan Ze University, Taoyuan 32003, Taiwan.
Biomedicines ; 12(3)2024 Feb 22.
Article en En | MEDLINE | ID: mdl-38540109
ABSTRACT
Glutamate is a major excitatory neurotransmitter that mediates neuronal damage in acute and chronic brain disorders. The effect and mechanism of phillygenin, a natural compound with neuroprotective potential, on glutamate release in isolated nerve terminals (synaptosomes) prepared from the rat cerebral cortex were examined. In this study, 4-aminopyridine (4-AP), a potassium channel blocker, was utilized to induce the release of glutamate, which was subsequently quantified via a fluorometric assay. Our findings revealed that phillygenin reduced 4-AP-induced glutamate release, and this inhibitory effect was reversed by removing extracellular Ca2+ or inhibiting vesicular transport with bafilomycin A1. However, exposure to the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate (dl-TOBA) did not influence the inhibitory effect. Moreover, phillygenin did not change the synaptosomal membrane potential but lowered the 4-AP-triggered increase in intrasynaptosomal Ca2+ concentration ([Ca2+]i). Antagonizing Cav2.2 (N-type) calcium channels blocked the inhibition of glutamate release by phillygenin, whereas pretreatment with the mitochondrial Na+/Ca2+ exchanger inhibitor, CGP37157 or the ryanodine receptor inhibitor, dantrolene, both of which block intracellular Ca2+ release, had no effect. The effect of phillygenin on glutamate release triggered by 4-AP was completely abolished when MAPK/ERK inhibitors were applied. Furthermore, phillygenin attenuated the phosphorylation of ERK1/2 and its major presynaptic target, synapsin I, a protein associated with synaptic vesicles. These data collectively suggest that phillygenin mediates the inhibition of evoked glutamate release from synaptosomes primarily by reducing the influx of Ca2+ through Cav2.2 calcium channels, thereby subsequently suppressing the MAPK/ERK/synapsin I signaling cascade.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomedicines Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomedicines Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza